Decreased inward rectifier and voltage-gated K⁺ currents of the right septal coronary artery smooth muscle cells in pulmonary arterial hypertensive rats
10.4196/kjpp.2020.24.1.111
- Author:
Sung Eun KIM
1
;
Ming Zhe YIN
;
Hae Jin KIM
;
Rany VORN
;
Hae Young YOO
;
Sung Joon KIM
Author Information
1. Department of Physiology, Seoul National University College of Medicine, Seoul 03080, Korea. physiolksj@gmail.com
- Publication Type:Original Article
- Keywords:
Coronary artery;
Inward rectifier K⁺ channel;
Pulmonary arterial hypertension;
Potassium channel;
Smooth muscle
- MeSH:
Animals;
Coronary Vessels;
Heart Diseases;
Heart Failure;
Hyperemia;
Hypertension;
Hypertrophy, Right Ventricular;
Ischemia;
Membrane Potentials;
Monocrotaline;
Muscle, Smooth;
Muscle, Smooth, Vascular;
Myocardium;
Myocytes, Smooth Muscle;
Patch-Clamp Techniques;
Potassium Channels;
Rats;
Septum of Brain
- From:The Korean Journal of Physiology and Pharmacology
2020;24(1):111-119
- CountryRepublic of Korea
- Language:English
-
Abstract:
In vascular smooth muscle, K⁺ channels, such as voltage-gated K⁺ channels (Kv), inward-rectifier K⁺ channels (Kir), and big-conductance Ca²⁺-activated K⁺ channels (BK(Ca)), establish a hyperpolarized membrane potential and counterbalance the depolarizing vasoactive stimuli. Additionally, Kir mediates endothelium-dependent hyperpolarization and the active hyperemia response in various vessels, including the coronary artery. Pulmonary arterial hypertension (PAH) induces right ventricular hypertrophy (RVH), thereby elevating the risk of ischemia and right heart failure. Here, using the whole-cell patch-clamp technique, we compared Kv and Kir current densities (I(Kv) and I(Kir)) in the left (LCSMCs), right (RCSMCs), and septal branches of coronary smooth muscle cells (SCSMCs) from control and monocrotaline (MCT)-induced PAH rats exhibiting RVH. In control rats, (1) I(Kv) was larger in RCSMCs than that in SCSMCs and LCSMCs, (2) I(Kv) inactivation occurred at more negative voltages in SCSMCs than those in RCSMCs and LCSMCs, (3) I(Kir) was smaller in SCSMCs than that in RCSMCs and LCSMCs, and (4) I(BKCa) did not differ between branches. Moreover, in PAH rats, I(Kir) and I(Kv) decreased in SCSMCs, but not in RCSMCs or LCSMCs, and I(BKCa) did not change in any of the branches. These results demonstrated that SCSMC-specific decreases in I(Kv) and I(Kir) occur in an MCT-induced PAH model, thereby offering insights into the potential pathophysiological implications of coronary blood flow regulation in right heart disease. Furthermore, the relatively smaller I(Kir) in SCSMCs suggested a less effective vasodilatory response in the septal region to the moderate increase in extracellular K⁺ concentration under increased activity of the myocardium.
